Neuraminidase inhibitors, superinfection and corticosteroids affect survival of influenza patients

Eur Respir J. 2015 Jun;45(6):1642-52. doi: 10.1183/09031936.00169714. Epub 2015 Jan 8.

Abstract

We aimed to study factors influencing outcomes of adults hospitalised for seasonal and pandemic influenza. Individual-patient data from three Asian cohorts (Hong Kong, Singapore and Beijing; N=2649) were analysed. Adults hospitalised for laboratory-confirmed influenza (prospectively diagnosed) during 2008-2011 were studied. The primary outcome measure was 30-day survival. Multivariate Cox regression models (time-fixed and time-dependent) were used. Patients had high morbidity (respiratory/nonrespiratory complications in 68.4%, respiratory failure in 48.6%, pneumonia in 40.8% and bacterial superinfections in 10.8%) and mortality (5.9% at 30 days and 6.9% at 60 days). 75.2% received neuraminidase inhibitors (NAI) (73.8% received oseltamivir and 1.4% received peramivir/zanamivir; 44.5% of patients received NAI ≤2 days and 65.5% ≤5 days after onset of illness); 23.1% received systemic corticosteroids. There were fewer deaths among NAI-treated patients (5.3% versus 7.6%; p=0.032). NAI treatment was independently associated with survival (adjusted hazard ratio (HR) 0.28, 95% CI 0.19-0.43), adjusted for treatment-propensity score and patient characteristics. Superinfections increased (adjusted HR 2.18, 95% CI 1.52-3.11) and chronic statin use decreased (adjusted HR 0.44, 95% CI 0.23-0.84) death risks. Best survival was shown when treatment started within ≤2 days (adjusted HR 0.20, 95% CI 0.12-0.32), but there was benefit with treatment within 3-5 days (adjusted HR 0.35, 95% CI 0.21-0.58). Time-dependent analysis showed consistent results of NAI treatment (adjusted HR 0.39, 95% CI 0.27-0.57). Corticosteroids increased superinfection (9.7% versus 2.7%) and deaths when controlled for indications (adjusted HR 1.73, 95% CI 1.14-2.62). Early NAI treatment was associated with shorter length of stay in a subanalysis. NAI treatment may improve survival of hospitalised influenza patients; benefit is greatest from, but not limited to, treatment started within 2 days of illness. Superinfections and corticosteroids increase mortality. Antiviral and non-antiviral management strategies should be considered.

Publication types

  • Observational Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Acids, Carbocyclic
  • Adrenal Cortex Hormones / therapeutic use*
  • Adult
  • Aged
  • Aged, 80 and over
  • Beijing / epidemiology
  • Cohort Studies
  • Cyclopentanes / therapeutic use
  • Enzyme Inhibitors / therapeutic use*
  • Female
  • Guanidines / therapeutic use
  • Hong Kong / epidemiology
  • Humans
  • Hydroxymethylglutaryl-CoA Reductase Inhibitors / therapeutic use*
  • Influenza, Human / mortality*
  • Male
  • Middle Aged
  • Multivariate Analysis
  • Neuraminidase / antagonists & inhibitors*
  • Oseltamivir / therapeutic use
  • Pneumonia, Bacterial / epidemiology*
  • Proportional Hazards Models
  • Prospective Studies
  • Protective Factors
  • Respiratory Insufficiency / epidemiology
  • Retrospective Studies
  • Risk Factors
  • Singapore / epidemiology
  • Superinfection / epidemiology*
  • Young Adult
  • Zanamivir / therapeutic use

Substances

  • Acids, Carbocyclic
  • Adrenal Cortex Hormones
  • Cyclopentanes
  • Enzyme Inhibitors
  • Guanidines
  • Hydroxymethylglutaryl-CoA Reductase Inhibitors
  • Oseltamivir
  • Neuraminidase
  • Zanamivir
  • peramivir